Title:  Conversion of liquid filled gelatin capsules into controlled release systems by multiple coatings

United States Patent:  6,419,952

Inventors:  Wong; Patrick S. -L. (Burlingame, CA); Dong; Liang C. (Sunnyvale, CA); Wan; Jiansheng (Palo Alto, CA)

Assignee:  Alza Corporation (Mountain View, CA)

Appl. No.:  866036

Filed:  May 25, 2001

A dosage form comprising a gelatin capsule formed with a composite wall and containing a liquid, active agent formulation where the wall comprises a barrier layer formed over the external surface of the gelatin capsule, an expandable layer formed over the barrier layer and a semipermeable layer formed over the expandable layer is described. The dosage forms and methods provide for the conversion of standard gelatin, liquid formulation capsules into controlled, release dosage forms that permit the controlled release of the active agent into the environment of use over time.

SUMMARY OF THE INVENTION

In one aspect, the invention comprises a dosage form comprising (a) a gelatin capsule containing a liquid, active agent formulation; (b) a multilayer wall superposed on the gelatin capsule comprising, in outward order from the capsule: (i) a barrier layer, (ii) an expandable layer, and (iii) a semipermeable layer; and (c) an orifice formed or formable through the wall.

In another aspect, the invention comprises a dosage form comprising a gelatin capsule containing a liquid, active agent formulation, the gelatin capsule being surrounded by a composite wall comprising a barrier layer contacting the external surface of the gelatin capsule, an expandable layer contacting the barrier layer, a semipermeable layer encompassing the expandable layer, and an exit orifice formed or formable in the wall.

In yet another aspect, the invention comprises a method of converting a gelatin capsule containing a liquid, active agent formulation into a controlled release dosage form which comprises forming a composite wall on the gelatin capsule by sequentially forming a barrier layer on the external surface of the gelatin capsule, an expandable layer on the barrier layer and a semipermeable layer on the expandable layer. An exit orifice may be formed in the wall directly, as by drilling, e.g., such as with a laser, or the exit orifice may be formed by sequentially forming an opening in the composite wall having a diametric dimension greater than the desired final diameter of the exit orifice, plugging the hole with a material in which the exit orifice may be formed, and then forming an exit orifice in the plug.

In still another aspect, the invention comprises a method of manufacturing a controlled release dosage form comprising a gelatin capsule containing a liquid, active agent formulation, which method comprises the steps of (1) forming a barrier layer surrounding the gelatin capsule containing a liquid, active agent formulation; (2) forming an expandable layer surrounding the barrier layer-gelatin capsule; (3) removing a portion of the expandable layer in an area in which an exit orifice is to be located without compromising the integrity of the barrier layer in the area; (4) forming a semipermeable layer surrounding the intermediate dosage form prepared through step (4); and forming an exit orifice in the area exposing at least a portion of the gelatin capsule. One or more of the layers may be formed by coating.

In yet another aspect, the invention comprises a dosage form comprising a gelatin capsule containing a liquid, active agent formulation, the gelatin capsule being surrounded by a composite wall comprising a barrier layer contacting the external surface of the gelatin capsule, an expandable layer contacting the barrier layer, a semipermeable layer encompassing the expandable layer, and an exit orifice formed or formable in the wall, wherein the barrier layer forms a seal between the expandable layer and the environment at the exit orifice.

In another aspect, the invention comprises a dosage form comprising a gelatin capsule containing a liquid, active agent formulation, the gelatin capsule being surrounded by a barrier layer contacting the external surface of the gelatin capsule, an expandable layer contacting a portion of the barrier layer, a semipermeable layer encompassing at least the expandable layer, and an exit orifice formed or formable in the dosage form extending from the external surface of the gelatin capsule to the environment of use. The expandable layer may be formed in one or more discrete sections, such as for example, two sections located on opposing sides or ends of the gelatin capsule.

Claim 1 of 20 Claims

What is claimed is:

1. A dosage form comprising (a) a gelatin capsule containing a liquid, active agent formulation; (b) a multilayer wall superposed on the gelatin capsule comprising, in outward order from the capsule: (i) a deformable barrier layer, (ii) an expandable layer, and (iii) a semipermeable layer; and (c) an orifice formed or formable through the wall.
 

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